Carbohydrate Based Therapeutics

John H. Musser Pharmagenesis, Inc. Palo Alto, California

Sixth Edition, Volume 2: Drug Development

Edited by Donald J. Abraham

ISBN 0-471-37028-2 © 2003John Wiley & Sons, Inc.

Contents

1 Introduction, 204

2 Carbohydrate-Based Drugs, 204

2.1 To Market-Last Decade, 205

2.1.1 Diabetes, 205

2.1.2 Gastrointestinal System, 206

2.1.3 Central Nervous System, 206

2.1.4 Infection, 207

2.1.5 Thrombosis, 209

2.1.6 Inflammation, 210

2.1.7 Enzyme Replacement, 211

2.2 Therapeutics in Development, 211

2.2.1 Gastrointestinal System, 212

2.2.3 Infection, 213

2.2.4 Thrombosis, 215

2.2.5 Inflammation, 216

2.2.6 Cancer, 216

2.2.7 Lysosomal Storage, 218

2.3 Agents in Research, 219

2.3.1 Diabetes, 219

2.3.2 Gastrointestinal System, 219

2.3.4 Infection, 221

2.3.5 Inflammation, 223

2.3.6 Cancer, 225

3 Carbohydrate Chemistry, 227

3.1 Chemistry, 227

3.1.1 Challenges and Opportunities, 227

3.1.2 Solution Phase, 227

3.1.3 Enzymatic, 229

3.1.4 Solid Phase, 230

3.1.5 Glycoprotein, 231

3.1.6 Carbohydrate Library, 231

3.2 Analysis, 232

3.2.1 Mass Spectrometry, 232

3.3 Natural Products Isolation, 232

3.4 Multivalency, 233

3.4.1 Viral Inhibitors, 233

3.4.2 RNA Target, 233

3.4.3 Toxin Inhibitors, 234 3.4.4Mechanism of Multivalency, 234

3.5 Heparin, 235

3.5.1Synthesis, 235 3.5.2 FGF, 235

3.5.3Heparin Analytical Tool, 236 4 Glycobiology, 236 4.1 Driving Forces, 236

4.1.1 Human Genome, 236

4.1.2 Therapeutic Glycoproteins, 237

4.1.3 Structure-Function, 237

4.2 Glycoconjugates, 237

4.2.1 Glycolipids, 237

4.2.2 Proteoglycans, 238

4.2.3 Glycoproteins, 238

4.3 Immunogens, 239

4.3.1 Immunoglobulins, 239

4.3.2 Hemagglutinins, 240

4.4 Lectins, 240

4.4.1 C-Type Lectins, 240

4.4.2 Mannan-Binding Lectin, 241 4.4.3Siglecs, 242

4.5 Health and Disease, 242

5 Summary—Continue the Pace, 242

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